Outcomes of patients with stage IB1 and IB2 Cervical Cancer who have had Wertheim's Hysterectomies with or without adjuvant chemo-radiotherapy as primary treatment at Charlotte Maxeke Johannesburg Academic Hospital

A research report submitted to the University of the Witwatersrand in partial fulfilment for the degree of Master of Medicine 2016.Background Cervical cancer is the 3rd most common female malignancy worldwide. It is classified and managed according to stage as defined by the FIGO Committee on Gynaecology Oncology classification of 2009. Stage specific treatment is tailored according to prognosis and risk of recurrence as determined by tumour type, tumour size, tumour grade, lymph node metastases, lymphovascular space involvement (LVSI), parametrial spread and presence of any other metastatic deposits at presentation. This study only concentrated on patients who presented with Stage IB1 and 1B2 tumours managed by Class III / Meig’s Radical / Wertheim’s hysterectomy and bilateral pelvic lymphadenectomy. Aims Primary Outcome 1. Assess disease free interval and overall survival 2 years post-operatively. Secondary Outcomes 1. Assess adequacy of patient selection 2. Assess risk factors for recurrence 3. Compare recurrence risk of HIV positive patients versus HIV negative patients. 4. Determine surgical and post-surgical complication rate. Materials and Methods This was a retrospective institutional cohort study conducted at the Charlotte Maxeke Johannesburg Academic Hospital. All patients with Stage IB1 or IB2 cervical cancer treated with Wertheim hysterectomies between 2002 and 2012 were included. Surgical records, histology records, further postoperative management records and gynaecological outpatient follow up records were used to collect data for the patients. Histological findings post-operatively determined further management. Surgical margins had to be 10mm clear of tumour with no positive lymph nodes otherwise external beam radiotherapy and brachytherapy or chemo-radiotherapy were recommended in addition to primary surgical management. Results Of the 72 patients initially identified, 69 patients were suitable for study inclusion. The mean age of the study population was 45 years. Study population racial distribution: 68.12% were Black, 26.09% were White, 2.9% were Coloured and 2.9% were Indian. Average parity and gravidity of patients alive at the end of the study was 2.86 and 3.56; while average parity and gravidity of patients deceased at the end of the study was 2.5 and 2.8 respectively. Study population ECOG status: 16% were ECOG 0, 83% were ECOG 1 and 1% were ECOG 2. Overall survival at the end of the study was 86% and patients were disease free postoperatively for an average of 5 years. Thirty three percent of the patients were disease free for more than 5 years. Preoperative clinical staging and postoperative histological staging correlated only in 61% of cases. Correct management by Wertheim’s hysterectomy was rendered to 75% of patients whereas the remainder were incorrectly managed and should have had either a simple hysterectomy with no pelvic lymphadenectomy or radiotherapy only as primary therapy. More advanced stages, tumours ≥ 4cm, adenomatous cell type, > 5mm depth of invasion, >7mm lateral spread, higher number of nodes positive for metastatic disease, surgical margins 10mm, positive lympohovascular space, parametrial and pouch of Douglas (POD) involvement were factors that had a poorer prognosis with regards overall survival, disease-free interval or both. Poorly differentiated tumours were more likely to recur but did not have a poorer prognosis compared with regards to overall survival or disease free interval at 2 or more years compared to well and moderately differentiated tumours. Mortality of HIV reactive patients was 16.7% compared to 12.5% for HIV non-reactive patients. This difference was not statistically significant at the 95% confidence level. HIV status also did not increase risk of recurrence. Lower CD4 counts were shown to have a lower disease-free period and overall survival. Intra-operative surgical complication rate was 6%. Immediate post-operative complication rate was 16%. Of the patients who required DXT or DXT and chemotherapy 33% had side-effects or complications from adjuvant therapy. Patients treated with DXT and chemotherapy had had more side-effects than those treated with DXT only. Conclusion The mean age of the study population was 45 years. This was lower compared to other larger studies possibly due to younger presentation related to HIV disease. HIV positive patients with lower CD4 counts were shown to have poorer prognosis with regards to survival. HIV status was not shown to be a risk factor for recurrence. The overall survival and disease-free period at 5 years was similar to that of other international studies. Only two thirds of the patients were adequately selected for surgery according to the institution’s criteria for a Wertheim’s hysterectomy and therefore it may be necessary to reconsider the pre-operative assessment of these patients. More advanced stages, tumours ≥ 4cm, adenomatous cell type, poor differentiation, > 5mm depth of invasion, >7mm lateral spread, higher number of nodes positive for metastatic disease, surgical margins ≤ 10mm, positive lympohovascular space, parametrial and pouch of Douglas involvement were factors that had a poorer prognosis with regards to recurrence, overall survival and disease-free interval. However, the rates of recurrence were not statistically significant at a 95% confidence level.LG201